Numerous dermatologic conditions are characterized by blister formation; (infections, allergic reactions, congenital abnormalities, i.e., epidermolysis bullosa and "autoimmune" bullous diseases). Considerable clinical and histopathologic data are available regarding these diseases but little is known about the ultimate molecular mechanism(s) involved in the pathophysiology of these conditions. In the present proposal a number of experiments are described for the study of pemphigus, bullous pemphigoid and epidermolysis bullosa from the point of view of the basic biological mechanisms involved in tissue injury. In vitro organ culture, epidermal suspension culture of fibroblasts monolayer culture will be used. Biochemical, light microscopic, immunofluorescent and electron-microscopic studies will be carried out. Pemphigus acantholysis produced in organ culture will be studied. In bullous pemphigoid the role of inflammatory cells in producing epidermal-dermal separation will be evaluated, while in epidermolysis bullosa dystrophica the nature of the dermal collagen(s) and glycosaminoglycans will be determined. Through a team effort, insight into the pathophysiology of these conditions with potential for practical therapeutic applications is expected. Insight into the synthesis and nature of intercellular cement substance of the epidermis and the nature of pemphigus and bullous pemphigoid antigens is also anticipated.